Although acetylcholine (Ach) and the cations Na ion and Ca ions have been implicated in the central (posterior hypothalamus) control of temperature regulation, their participation in the control of specific effector responses has not been studied. This proposal directly addresses this problem both at rest and during exercise using the Rhesus monkey as an exprimental model. These animals closely resemble man in their effector responses to thermal stimuli and can be exercised in a quantitative fashion under sufficient restraint to permit delicate manipulations of the brain. Each animal is acclimated to a primate chair and trained on a "rowing machine" to avoid shock. The experimental protocol consists of 30 min rest, 30-60 min of exercise at a given % of max VO2, and 60 min recovery. Measurements will include heart rate, skin and colonic temperatures, sweat rate by resistance hygrometry, and oxygen uptake using a continuous open flow draw system. Effects of Ach on sweat rate, metabolic rate, and tissue heat conductance will be determined by microinjections of cholinergic agonists, antagonists, and receptor blockers into the posterior hypothalamus (PH). To evaluate cation effects, Na ion/Ca ions ratios will be altered in mock CSF delivered to the PH by push-pull perfusion. To further illucidate Ca ions kinetics, the effects of (a) blocking Ca ions entry into the PH cells with tetrodotoxin and verapamil, (b) blocking Ca ions efflux with ouabain, and (c) inducing Ca ions channels with the ionophore A23187 will also be determined. In addition, the endogenous activity of 14C-Ach, 45Ca ions, and 22Na in the PH during exercise will be determine by radiolabelling the brain via an intraventricular injection and monitoring the washout curve of radioactivity. The significance of this proposal is twofold: (a) it enables the study, for the first time, of the central mechanisms involved in exercise thermoregulation in a model resembling man, and (b) the model provides for the measurement of effector responses as the output of the thermoregulatory system and not simply a change in body temperature which has so often been used in studies of this nature.